| Autor: |
Megan L. Gliozzi, Youssef Rbaibi, Dario A. Vitturi, Jesús Tejero, Ora A. Weisz |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
|
| Zdroj: |
Journal of Clinical and Translational Science, Vol 3, Pp 12-13 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
2059-8661 |
| DOI: |
10.1017/cts.2019.32 |
| Popis: |
OBJECTIVES/SPECIFIC AIMS: While Hb-induced toxicity has been assumed to cause PT dysfunction, the development of tubular proteinuria from this dysfunction in SCD patients is not well understood. We previously found that free Hb, at concentrations predicted to be present chronically and during hemolytic crisis in the tubular filtrate of SCD patients, impairs uptake of albumin by PT cells via direct competition for binding to megalin and cubilin receptors. The purpose of this study is to further evaluate the consequences of increased filtered Hb concentrations on vitamin D reabsorption and activation. METHODS/STUDY POPULATION: We have developed a PT cell culture model that closely mimics in vivo PT cell structure, morphology, and endocytic capacity. Using this model, we treated cells with physiologic levels of cell-free Hb estimated in SCD and measured protein endocytosis and toxicity/oxidative stress. Endocytosis of fluorescently-tagged DBP and RBP were evaluated and quantified by confocal imaging and spectrofluorometry. Cellular toxicity and oxidative stress were assessed by measuring aconitase activity and accumulation of mitochondrial reactive oxygen species. RESULTS/ANTICIPATED RESULTS: PT cell uptake of DBP was significantly inhibited by both concentrations of Hb estimated to be filtered into the tubule lumen under chronic conditions (0.6μM Hb; 39% inhibition) and hemolytic crisis (≤20μM Hb; up to 92% inhibition) in SCD patients. ****p |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
